D-dimer: Simple Test, Tough Problems

Abstract

Context.-D-dimer is widely used for exclusion, or as an aid in diagnosis, of venous thromboembolism (VTE); however, the D-dimer assay methods available from manufacturers and the laboratory application of those methods vary widely.Objective.-To describe the current laboratory practice regarding the assay and reporting of D-dimer.Design.-Laboratories' D-dimer proficiency testing data were analyzed and laboratory practices regarding the performance and reporting of D-dimer were surveyed.Results.-Initial grading of D-dimer proficiency testing demonstrated high variability within and among methods. This variability continued to be present for several years after attempts to intervene. The number of laboratories using D-dimer to exclude VTE grew from 1500 in 2004 to more than 3500 in 2012. Survey and proficiency testing data demonstrated that 33% of laboratories changed the type or magnitude of units from that recommended by the manufacturer, a practice associated with as much as a 20-fold increase in the failure of proficiency testing. Many laboratories used a threshold for the exclusion of VTE that is higher than that recommended by the manufacturer. Many laboratories continue to use qualitative assays with insufficient sensitivity for exclusion of VTE.Conclusions.-There is considerable variability both within and among quantitative methods used to assay Ddimer by laboratories. Laboratory practice continues to vary widely regarding the type and magnitude of units reported and the setting of the threshold for the exclusion of VTE. Although improved, the variability continues despite initial efforts to intervene.

Methods available to assess therapeutic potential of fibrinolytic enzymes of microbial origin: a review

“…These fibrin monomers self-assemble into fibres and get covalently cross-linked at the outer 2D domains of the adjacent fibrin monomers and the central E domain of the third fibrin monomer. Later, the enzyme plasmin cleaves the crosslinked fibrin polymer at various sites resulting in the release of D-dimer fragments (XDPs) (Olson et al 2013). Some of the commercially available assays used to detect these XDPs are latex agglutination, immunoturbidimetry and enzyme-linked immunosorbent assay (ELISA).…”

“…The presence of D-dimers indicates the occurrence of fibrinolysis due to the plasmin-like action of the test compound. The D-dimer is usually reported as mass units, and there are two different types of units: the fibrinogen equivalent unit (FEU) at 340 kDa and the D-dimer unit (DDU) at 195 kDa (Olson et al 2013).…”

“…The applicability of the D-dimer test helps in determining the duration of the anticoagulation therapy serves as an advantage (Olson et al 2013). During medical conditions such as arterial, venous thrombosis and pulmonary embolism, the D-dimer levels are elevated (Mavromatis and Kessler 2001;Wakai et al 2003;Adam et al 2009).…”

“…During medical conditions such as arterial, venous thrombosis and pulmonary embolism, the D-dimer levels are elevated (Mavromatis and Kessler 2001;Wakai et al 2003;Adam et al 2009). However, few of the drawbacks associated with this assay are (i) its variation with respect to the types of D-dimer unit that differ with onefold difference in mass and the magnitude of units reported clinically leads to confusion, particularly when this assay is used to exclude conditions such as venous thromboembolism; (ii) this assay is not applicable for fibrinogenolysis, as the derivatives of fibrinogen degradation lack D-domain despite being present in high concentration; and (iii) it has also been reported that the various quantitative D-dimer assays currently in use vary in their reproducibility (Olson et al 2013). …”

Policies and practices in haemostasis testing among laboratories in Croatia: a survey on behalf of a Working Group for Laboratory Coagulation of the Croatian Society of Medical Biochemistry and Laboratory Medicine

“…Evidences obtained in both surveys underline the need for further standardization in D-dimer result reporting. In general, D-dimer testing lacks standardization all over the world since there is still no standardized measurement unit, unique monoclonal antibody and calibrator ( 32 , 33 ). Thus results, RI and clinical cut-off values cannot be extrapolated between methods.…”